title: BAFF maintains T-cell survival by inducing OPN expression in B cells.
abstract: Dysregulation of T-cell survival and apoptosis is the common cause of autoimmune diseases such as multiple sclerosis (MS). However, the factors inducing imbalance of T-cell survival and apoptosis in MS remains unclear. Here, we show that the resistance to apoptosis was associated with high levels of B-cell activating factor (BAFF). Blockade of BAFF with TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor)-IgG significantly reduced T-cell survival in myelin oligodendroglia glycoprotein (MOG)-induced chronic experimental allergic encephalitis (EAE). Furthermore, BAFF induced anti-apoptotic molecule Bcl2 expression in T cells by up-regulating osteopontin (OPN) secretion from B cells. BAFF mainly induced OPN expression in splenic CD21(-)CD23(+) B cells via a NF-kB dependent signaling pathway. In addition, we found that BAFF and OPN levels were increased in MS patients similar to the results obtained from our mice research. The study suggests that BAFF regulates T-cell survival by inducing OPN secretion in B cells in autoimmune diseases.
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China; Department of Rheumatology, First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Youdi
authors.initials: Y
authors.lastname: He
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.forename: Guojiang
authors.initials: G
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Chunmei
authors.initials: C
authors.lastname: Hou
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yang
authors.forename: Bernadette
authors.initials: B
authors.lastname: Marrero
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Renxi
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D053264:B-Cell Activating Factor / Q000096:biosynthesis / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D053495:Osteopontin / Q000096:biosynthesis / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology; D017464:Receptors, Complement 3d / Q000096:biosynthesis; D017455:Receptors, IgE / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000276:immunology / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D063308:Myelin-Oligodendrocyte Glycoprotein; D016328:NF-kappa B; D010446:Peptide Fragments; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; C486361:Tnfrsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; C445081:myelin oligodendrocyte glycoprotein (35-55); D053495:Osteopontin
keywords: BAFF; EAE; OPN; T cells